Abstract:
:The identification of a biologic substrate for maintaining hepatocyte functions is essential to provide reliable and predictable models for in vitro drug screening. In the current study, a three-dimensional culture of hepatocytes was established on highly porous fibrous scaffolds with grafted galactose and RGD to afford extensive cell-cell and cell-scaffold interactions spatially. The pore size and ligand densities indicated significant effects on the formation of hepatocyte spheroids in balancing the cell retention, adhesion, and migration on fibrous scaffolds. Fibrous scaffolds with an average pore size of 60 μm and surface grafting densities of galactose at 5.9 nmol/cm(2) and RGD at 6.9 pmol/cm(2) provided optimal microenvironments for hepatocyte infiltration and multicellular spheroid formation. Significant promotions were also demonstrated in the syntheses of albumin and urea and the activities of phase I (CYP 3A11 and CYP 2C9) and phase II enzymes. The in vitro metabolism tests on testosterone and acetaminophen by hepatocytes on the optimal scaffolds indicated the predicated clearance rates of 50.7 and 22.6 ml/min/kg, respectively, which were comparable to the in vivo values of rats. The in vitro hepatotoxicity tests on amiodarone hydrochloride and acetaminophen predicted the half maximal effective concentrations (EC50) to reflect the in vivo toxic plasma concentrations in human. In addition, the enzyme activities, predicted clearance rates and hepatotoxicity values of hepatocytes on the optimal scaffolds experienced sensitive responsiveness to specific inducers or inhibitors of CYP 3A11 and phase II enzymes, exhibiting in vivo-in vitro correlations to a certain extent. These results demonstrate the feasibility of hepatocyte spheroid culture on fibrous scaffolds as an potential in vitro testing model to predict the in vivo drug metabolism, hepatotoxicity, and drug-drug interactions.
journal_name
Acta Biomaterjournal_title
Acta biomaterialiaauthors
Yan S,Wei J,Liu Y,Zhang H,Chen J,Li Xdoi
10.1016/j.actbio.2015.09.027subject
Has Abstractpub_date
2015-12-01 00:00:00pages
138-148eissn
1742-7061issn
1878-7568pii
S1742-7061(15)30120-3journal_volume
28pub_type
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journal_title:Acta biomaterialia
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journal_title:Acta biomaterialia
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journal_title:Acta biomaterialia
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journal_title:Acta biomaterialia
pub_type: 杂志文章
doi:10.1016/j.actbio.2019.10.013
更新日期:2019-12-01 00:00:00
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journal_title:Acta biomaterialia
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journal_title:Acta biomaterialia
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journal_title:Acta biomaterialia
pub_type: 杂志文章
doi:10.1016/j.actbio.2009.12.022
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journal_title:Acta biomaterialia
pub_type: 杂志文章
doi:10.1016/j.actbio.2013.06.017
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journal_title:Acta biomaterialia
pub_type: 杂志文章
doi:10.1016/j.actbio.2011.09.027
更新日期:2012-01-01 00:00:00
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pub_type: 杂志文章
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更新日期:2010-06-01 00:00:00
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journal_title:Acta biomaterialia
pub_type: 杂志文章
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更新日期:2020-01-15 00:00:00
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journal_title:Acta biomaterialia
pub_type: 杂志文章
doi:10.1016/j.actbio.2010.07.017
更新日期:2011-01-01 00:00:00
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journal_title:Acta biomaterialia
pub_type: 杂志文章
doi:10.1016/j.actbio.2014.11.031
更新日期:2015-02-01 00:00:00
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journal_title:Acta biomaterialia
pub_type: 杂志文章
doi:10.1016/j.actbio.2015.06.005
更新日期:2015-09-01 00:00:00
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journal_title:Acta biomaterialia
pub_type: 杂志文章
doi:10.1016/j.actbio.2017.03.016
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journal_title:Acta biomaterialia
pub_type: 杂志文章
doi:10.1016/j.actbio.2009.03.007
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journal_title:Acta biomaterialia
pub_type: 杂志文章
doi:10.1016/j.actbio.2009.12.013
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journal_title:Acta biomaterialia
pub_type: 杂志文章
doi:10.1016/j.actbio.2019.11.026
更新日期:2020-01-15 00:00:00
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journal_title:Acta biomaterialia
pub_type: 杂志文章
doi:10.1016/j.actbio.2012.04.019
更新日期:2012-08-01 00:00:00
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journal_title:Acta biomaterialia
pub_type: 杂志文章
doi:10.1016/j.actbio.2014.11.029
更新日期:2015-02-01 00:00:00
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journal_title:Acta biomaterialia
pub_type: 杂志文章
doi:10.1016/j.actbio.2016.05.003
更新日期:2016-07-15 00:00:00
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journal_title:Acta biomaterialia
pub_type: 杂志文章
doi:10.1016/j.actbio.2017.01.008
更新日期:2017-03-01 00:00:00
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journal_title:Acta biomaterialia
pub_type: 杂志文章
doi:10.1016/j.actbio.2018.09.020
更新日期:2018-10-15 00:00:00
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journal_title:Acta biomaterialia
pub_type: 杂志文章
doi:10.1016/j.actbio.2019.06.030
更新日期:2019-09-01 00:00:00
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journal_title:Acta biomaterialia
pub_type: 杂志文章
doi:10.1016/j.actbio.2020.06.005
更新日期:2020-09-01 00:00:00
abstract:UNLABELLED:The regeneration of hyaline cartilage remains clinically challenging. Here, we evaluated the therapeutic effects of using cell-free porous poly(lactic-co-glycolic acid) (PLGA) graft implants (PGIs) along with early loading exercise to repair a full-thickness osteochondral defect. Rabbits were randomly alloca...
journal_title:Acta biomaterialia
pub_type: 杂志文章
doi:10.1016/j.actbio.2015.09.026
更新日期:2015-12-01 00:00:00